CN117481699A - Evaluation method for relieving efficacy of sensitive skin product and application thereof - Google Patents
Evaluation method for relieving efficacy of sensitive skin product and application thereof Download PDFInfo
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Classifications
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- G—PHYSICS
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- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0035—Vaccination diagnosis other than by injuring the skin, e.g. allergy test patches
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/44—Detecting, measuring or recording for evaluating the integumentary system, e.g. skin, hair or nails
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Abstract
The invention discloses an evaluation method for relieving efficacy of sensitive skin products and application thereof, belonging to the technical field of analysis and detection; the establishment process of the evaluation method provided by the invention comprises the following steps: the forearm skin of the subject is treated by combining tape stripping and capsaicin patch to simulate the damaged state of the sensitive face, and skin redness (a) and transepidermal water loss (TEWL) are taken as main detection indexes to evaluate the soothing effect of the cosmetic for sensitive skin. The method can replace the facial capsaicin patch test, and has simpler, milder and more effective operation; meanwhile, the method fully considers the willingness of the subject, greatly reduces the anxiety of the subject about change of appearance in the detection process, and has wider applicability. The invention has better practical significance and application value.
Description
Technical Field
The invention belongs to the technical field of analysis and detection, and particularly relates to an evaluation method for relieving efficacy of sensitive skin products and application thereof.
Background
Sensitive skin is defined as the human self-reported different sensory perceptions of the presence of the face, including redness, itching, burning, and possibly accompanied by a redness response to stimulus. Studies have shown that sensitive skin is the result of impaired barrier function, leading to a significant response of the skin to other harmless stimuli. Sensitive skin is also a potential cause of certain skin diseases, such as psoriasis, acne, rosacea, etc., where the prevalence of sensitive skin in rosacea patients can be as high as 100%. In addition, research into sensitive skin is widely focused because of the increased global prevalence of sensitive skin due to age, lifestyle, and geographical environmental impact.
Sensory nerve dysfunction is an important pathological mechanism of sensitive skin, in which transient receptor potential vanilloid subfamily member 1 (TRPV 1) is expressed to be enhanced in skin-sensitive subjects, which changes are highly correlated with sensitive skin symptoms. TRPV1 is a non-selective cation channel belonging to the Transient Receptor Potential (TRP) channel family, which can be expressed in nociceptive neurons and non-neuronal cells such as keratinocytes, fibroblasts and endothelial cells as a detector of harmful stimuli, and is a key target for the treatment of sensitive skin. Capsaicin is a natural activator of TRPV1, and can be applied to sensitive skin evaluation and cosmetic efficacy evaluation and sensitivity measurement for inter-nasal-labial skin, and topical application of capsaicin has been truly a stable model for testing skin nerve sensitivity.
Currently, evaluating the soothing efficacy of cosmetics on sensitive skin based on the face causes abnormal sensations, erythema and skin barrier lesions, producing intolerable unpleasant sensations, and therefore the method of using capsaicin patches on the face has low applicability in sensitive skin populations, especially in moderately highly sensitive skin populations. The assessment of sensitive skin characterized by subjective unpleasant sensations and the development of soothing actives remain challenging.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide an evaluation method for the relieving efficacy of sensitive skin products, which has the advantages of simple operation, good stability, high accuracy, good applicability and high acceptance of subjects, and the application thereof.
To achieve the above object, in a first aspect of the present invention, there is provided a method of evaluating the soothing efficacy of a sensitive skin product, the method comprising the steps of:
(1) Randomly selecting a skin test area on the forearm of a subject, and testing redness and transepidermal water loss of the skin test area;
(2) Sequentially using adhesive tape stripping and capsaicin patch to treat the skin test area, standing for one time after treatment, and testing redness and transepidermal water loss of the skin test area after one-time standing;
(3) Smearing sensitive skin products on the skin test area after primary standing, and after smearing, carrying out secondary standing to test redness and transepidermal water loss of the skin test area after secondary standing;
(4) Comparing and calculating the redness and the transepidermal water loss obtained by the test in the step (3) and the step (1) to obtain a first numerical value of the redness and the transepidermal water loss of the skin test area; and/or calculating the redness and the transepidermal water loss obtained by the tests in the step (3) and the step (2) to obtain a second numerical value of the redness and the transepidermal water loss of the skin test area;
(5) Evaluating the soothing efficacy of the product according to the first value and/or the second value;
in the step (2), the number of times of stripping the adhesive tape is 2-15 times;
the application time of the capsaicin patch is 2-15min.
Skin sensitivity can currently be assessed in three ways: visible signs of irritation scoring, subjective response assessment, and skin function testing. Irritation signs scoring can be seen visually for erythema and edema; subjective reactivity tests use qualitative scales to measure the degree of discomfort caused by different stimuli and rely on the volunteer's spoken response; skin function tests were developed as objective substitutes for neurosensory tests, using different non-invasive methods to detect skin properties, such as transepidermal water loss (TEWL). Research shows that the three modes are mutually dependent, and almost no parameters can be kept unchanged within a certain range in the test process. Therefore, the accuracy and the stability of the method are judged by taking the data result of the daily practical application part (facial skin) of the cosmetics as a reference.
According to the evaluation method of the soothing effect of the cosmetics for sensitive skin, provided by the invention, the sensitive skin injury model of the face is simulated by combining tape stripping and capsaicin patch, and the forearm skin of a subject is sequentially treated by tape stripping and capsaicin patch, and the appropriate tape stripping times and the capsaicin patch application time are selected in combination with the investigation of the intention of the subject, so that the problem that the acceptance degree is low due to the fact that the face is directly adopted as a tested part in the evaluation of the soothing effect of the cosmetics for sensitive skin, and the capsaicin patch treatment is directly carried out on the face skin, so that the subject is difficult to bear test pain or the adverse effect on the change of the appearance of capsaicin after the use is worried can be avoided. The establishment result of the invention has high consistency with the facial capsaicin patch evaluation, and the high consistency is reflected in the establishment process of a sensitive skin injury state model in the early stage, namely, the high consistency is maintained by combining the redness degree of the forearm skin and the value of the transepidermal water loss before and after the tape stripping and the capsaicin patch treatment with the facial capsaicin patch evaluation in the establishment process of the sensitive skin injury state; on the other hand, the redness of the front arm skin and the face skin and the variation of the transepidermal water loss are also kept highly consistent before and after the use of the sensitive skin cosmetics; namely, the method for evaluating the soothing effect of the cosmetics for sensitive skin provided by the invention can effectively evaluate the soothing effect of the active substances on the sensitive skin, and the improvement condition of the sensitive skin is more visual. The high consistency also shows that the method provided by the invention has higher accuracy; meanwhile, the method provided by the invention is simple to operate and good in stability, can reduce the stinging and uncomfortable feeling in the evaluation process as much as possible, has little damage to skin, and is milder, so that the safety worry of a test method and anxiety about change of appearance of a test subject can be reduced, the test will of the test subject is obviously improved, and the acceptability is high. In addition, the evaluation method of the soothing efficacy of the sensitive skin cosmetic can solve the problem of low acceptance caused by the conventional evaluation using the face, and can achieve the effect of rapidly evaluating the soothing efficacy of the sensitive skin cosmetic.
In particular, tape stripping is a method for uniformly reducing the thickness of the skin horny layer, and the sensitivity of the skin to the capsaicin patch can be improved by using the tape stripping before applying the capsaicin patch, and although the tape stripping can not completely remove the horny layer, it can be confirmed that more horny layer is removed with the increase of the stripping period, so that the sensitivity of the skin to be tested to the capsaicin patch can be remarkably improved; capsaicin, a common component found in fruits of plants of the genus Capsicum, is a common potent activator of the TRPV1 channel, permeable to Ca 2+ Is an ion channel of the composition, and the topical capsaicin can cause burning pain; the adhesive tape stripping and capsaicin patch are combined, the tested area is selected as the forearm, pain nerves at the skin of the forearm are not developed as those of the facial skin, so that the acceptance of a subject can be improved, the sensitivity at the skin of the forearm can be consistent with that of the facial skin to a certain extent, the pain feeling of the subject can be reduced on the basis of ensuring reliable and accurate results, and the application range can be improved.
The adhesive tape used in the invention is a medical adhesive tape.
The product in the sensitive skin product is a cosmetic; the cosmetic comprises toning lotion, cosmetic milk, essence, facial mask and face cream, and also comprises individual active ingredients or active components.
The redness (a) of the skin according to the present invention is measured by a colorimeter CL 400; the inventive test of transepidermal water loss (TEWL) of skin is usedThe test was conducted on TM Hex (Coura+Khazaka).
Wherein, the first value is redness or change rate of transepidermal water loss, and the specific calculation method of the first value is as follows: skin redness (a) change rate= (skin redness after secondary standing-skin redness before treatment)/skin redness before treatment x 100%; rate of change of skin transepidermal water loss (TEWL) = (skin transepidermal water loss after secondary resting-skin transepidermal water loss before treatment)/skin transepidermal water loss before treatment x 100%.
The second value is the redness or the change rate of the transepidermal water loss, and the specific calculation method of the second value is as follows: skin redness (a) change rate= (skin redness after secondary rest-skin redness after primary rest)/skin redness after primary rest x 100%; skin transepidermal water loss (TEWL) change rate= (skin transepidermal water loss after secondary resting-skin transepidermal water loss after primary resting)/skin transepidermal water loss after primary resting x 100%.
Meanwhile, the invention can also test the changes of skin redness and transepidermal water loss with time in the step (2) and the step (3), namely a numerical value three (A) and a numerical value three (B), wherein the numerical value three (A) is calculated by the method: skin redness change amount = (skin redness after one rest-skin redness after one rest for X min) X (-1); skin transepidermal water loss (TEWL) change amount= (skin transepidermal water loss after one rest-skin transepidermal water loss after one rest for X min) X (-1); the value three (a) was also used to evaluate the relief of the skin in its natural state.
The calculation method of the numerical value three (B) is as follows: skin redness change amount = (skin redness after secondary standing-skin redness after primary standing) × (-1); skin transepidermal water loss (TEWL) change amount= (skin transepidermal water loss after secondary rest-skin transepidermal water loss after primary rest) × (-1).
Meanwhile, the invention can calculate the redness of skin and the value of transepidermal water loss before treatment and after one-time standing, which are marked as four values, wherein the four values are the change rate of redness or transepidermal water loss, and the calculation method comprises the following steps: skin redness (a) change rate= (skin redness after one standing-skin redness before treatment)/skin redness before treatment x 100%; rate of change of skin transepidermal water loss (TEWL) = (skin transepidermal water loss after one rest-skin transepidermal water loss before treatment)/skin transepidermal water loss before treatment x 100%. The larger the a and TEWL values in the four values represent the greater the extent of skin damage, the pre-treatment a and TEWL refer to the data obtained by the test of step (1).
Specifically, the numerical value III (A) provided by the invention can judge whether the physiological states of the arms and the faces are consistent before and after treatment; the magnitude of the numerical value I and the numerical value III (B) provided by the invention can qualitatively reflect the relieving effect of the cosmetic on sensitive skin, for example, if the numerical value of the numerical value III (B) of redness is larger, the relieving effect on the redness of the sensitive skin after the relieving product is coated is stronger, and the cosmetic has a certain effect on the sensitive skin; if the value of redness is 0, the skin can be restored to the initial state after the product is used; in addition, the numerical value one and the numerical value three (B) can be used for judging the magnitude of the soothing efficacy of two or more cosmetics on sensitive skin.
The provision of the fourth value can confirm whether the established forearm model has good consistency with the face, and experiments prove that the fourth value has high consistency with the skin redness and the transepidermal water loss after the face uses the capsaicin patch, so that the evaluation method can well replace the face capsaicin patch evaluation method; the provision of the first value, the third value (A) and the third value (B) can further confirm whether the trend after the application of the sensitive skin cosmetics has good consistency with the trend of the face evaluation method, and experiments prove that the first value is also highly consistent with the trend after the application of the corresponding sensitive skin cosmetics after the face application of the capsaicin patch; from the comparison of the two values and the change trend of the face, the method provided by the invention can be clearly known to replace the existing face capsaicin patch evaluation method.
At the same time, the invention fully incorporates the subject's condition, collecting subject test willingness and semi-subjective volunteer scores. Wherein semi-subjective pain may be divided into 5 scores, including 0=no sensation, 1=almost sensation, 2=mild sensation, 3=moderate sensation, 4=severe sensation, 5=pain.
As a preferred embodiment of the evaluation method of the present invention, the skin test area is selected from the skin at the inner side of the forearm.
Preferably, the skin test area is selected to avoid skin in densely distributed areas of the blood vessels inside the forearm.
The inventor researches find that the specific selected skin position to be tested also has a certain influence on the accuracy of the evaluation method, and a large number of experiments by the inventor prove that when the skin of the selected subject is the skin on the inner side of the forearm, especially the skin on the inner side of the forearm, which avoids the dense distribution area of blood vessels, the consistency between the result obtained by the test and the result obtained by the facial capsaicin patch test is better, and the measured values of the selected areas are not different and are not influenced by the skin areas.
As a preferred embodiment of the evaluation method of the present invention, the number of times of tape stripping is 2 to 10.
As a preferred embodiment of the evaluation method of the present invention, the number of times of tape stripping is 5 to 10.
Preferably, the number of times the tape is peeled off is 5.
The adhesive tape stripping can uniformly reduce the thickness of the skin cuticle, and the inventor researches and discovers that when the number of times of the adhesive tape stripping is limited to 5-10 times, the accuracy of the obtained evaluation method is better, and the subjective intention of a subject can be considered; meanwhile, the inventor researches that the frequency of tape stripping and the accuracy of the result are not in linear change, and excellent comprehensive effect can be obtained only when the frequency is within the range given by the invention; in particular, the number of times of stripping the adhesive tape is further selected to be 5-10 times, and the obtained comprehensive effect is optimal when the number of times of stripping the adhesive tape is further selected to be 5 times.
As a preferred embodiment of the evaluation method of the present invention, the capsaicin patch is prepared by: immersing the filter paper sheet into ethanol water solution containing capsaicin, taking out, and using to obtain capsaicin patch
The filter paper sheet is square membrane cloth, has good permeability and absorbability, and can be directly applied to the surface of skin.
The filter paper is used as the bearing component, the capsaicin is prepared into a patch form, and the distribution uniformity of the capsaicin at the skin to be tested can be ensured, so that the accuracy of the result is improved.
As a preferred embodiment of the evaluation method of the present invention, the capsaicin-containing aqueous ethanol solution has a capsaicin content of 0.005-0.03% by mass.
As a preferred embodiment of the evaluation method of the present invention, the capsaicin-containing aqueous ethanol solution has a capsaicin content of 0.01% by mass.
The mass percent of capsaicin in aqueous ethanol solutions containing capsaicin directly correlates to the concentration of capsaicin in the patch, a common potent activator of TRPV1 channels, permeable Ca 2+ The inventor has proved by a large number of experiments that when the mass percentage of the capsaicin selected is 0.005-0.03%, the accuracy and stability of the evaluation method can be ensured, the acceptability of the subject can not be damaged, namely the comprehensive effect is excellent, and especially when the mass percentage of the capsaicin is further selected to be 0.01%, the comprehensive effect of the obtained evaluation method is optimal.
As a preferred embodiment of the evaluation method of the present invention, the volume ratio of ethanol to water in the capsaicin-containing aqueous ethanol solution is ethanol: water= (5-15): (85-95).
Preferably, in the capsaicin-containing ethanol aqueous solution, the volume ratio of ethanol to water is ethanol: water = 10:90.
since capsaicin is insoluble in water, it is dissolved in aqueous ethanol, further defining the volume ratio of ethanol to water in aqueous ethanol as ethanol: water= (5-15): (85-95), the influence on skin irritation caused by excessive organic solvent residues can be avoided on the basis of ensuring capsaicin dissolution, so that the accuracy of the evaluation method is influenced; in particular, the volume ratio of ethanol to water is further selected as ethanol: water = 10: at 90, the effect of residual ethanol can be minimized.
As a preferred embodiment of the evaluation method of the present invention, the capsaicin patch is applied for 2 to 10 minutes.
As a preferred embodiment of the evaluation method of the present invention, the capsaicin patch is applied for 5 to 10 minutes.
The application time of the capsaicin patch can influence the application time of the capsaicin to the skin, and the inventor researches and discovers that the accuracy and the stability of the evaluation method can be effectively improved when the application time is 2-10min, especially 10min.
As a preferred embodiment of the evaluation method of the present invention, the one-time standing time is 5 to 20 minutes.
As a preferred embodiment of the evaluation method of the present invention, the one-time standing time is 5 to 10 minutes.
The inventor researches and discovers that the accuracy of the evaluation method can be improved when the redness and the transepidermal water loss of the skin after the treatment are tested within the range of one-time standing time period, and particularly the numerical value obtained by testing and calculating in 10 minutes is highly consistent with the result of the facial capsaicin patch test.
As a preferred embodiment of the evaluation method of the present invention, the time for the secondary standing is 10 to 40 minutes.
The inventor researches that the measurement is carried out for 10-40min after the sensitive skin cosmetics are applied, so that the cosmetics can be given a certain action time, and the reliability of the result obtained by the measurement is better.
As a preferred embodiment of the evaluation method of the present invention, the treatment is carried out at an ambient temperature of 20-25℃and a relative humidity of 40-60%.
The inventor researches and discovers that the change of the treated environmental temperature and humidity not only can influence the skin state of a subject, but also can influence the permeation rate of capsaicin during capsaicin patch, so that the reliability of an evaluation method is further influenced from multiple aspects, and when the treated environmental temperature and humidity are selected to be within the temperature and humidity range of the invention, the accuracy and stability of the evaluation method can be improved as a whole by further matching with certain tape stripping times, capsaicin patch application time and treated standing time.
In a second aspect of the invention, the invention provides the use of a method for evaluating the soothing efficacy of a cosmetic for sensitive skin in a soothing active product.
Compared with the prior art, the invention has the beneficial effects that:
(1) The result obtained by the evaluation method aiming at the relieving efficacy of the sensitive skin product has high consistency with the evaluation method of the capsaicin patch applied to the face, namely the method provided by the invention has higher accuracy; meanwhile, the method provided by the invention has good stability, can reduce the stinging and uncomfortable feeling in the evaluation process as much as possible, has little damage to skin, and is milder, so that the safety worry of a test method and anxiety about change of appearance of a test subject can be reduced, the test will of the test subject is obviously improved, and the acceptability is high;
(2) The evaluation method for the relieving efficacy of the sensitive skin product provided by the invention has the advantages of low test cost, no need of additional instruments and equipment, simple and easy operation process, low requirement on operators, more visual result and capability of accurately reflecting the real condition of human skin;
(3) The evaluation method for the soothing efficacy of the sensitive skin product detects the skin redness and the transepidermal water loss of the subject to quantify the soothing effect of the cosmetics, fully brings in the semi-self subjective pain score of the subject, has good consistency with the evaluation result of the facial capsaicin patch test in the prior art, and can effectively replace the facial patch test, thereby establishing a model for simulating the response of the face to the nerve stimulation;
(4) The evaluation method for the relieving efficacy of the sensitive skin product can also be used for preparing the active cosmetics for evaluating the efficacy of the active cosmetics so as to guide the development of the active cosmetics, and has good practical significance and application value.
Drawings
FIG. 1 is a practical explanatory view of a skin region on the inner side of the forearm in effect example 1;
FIG. 2 is a schematic diagram of the test flow in effect example 1;
fig. 3 is a graph showing the results in effect example 3:
a is a trend graph of a with time in test example 2,
b is a trend graph of TEWL over time in test example 2,
c is a histogram of values of a and TEWL at T0' in test example 2,
d is a trend graph of a with time in example 1,
e is a trend of TEWL over time in example 1,
f is a histogram of values for a and TEWL at T0' in example 1,
g is a trend graph of a in test example 5 over time,
h is a trend graph of TEWL over time in test example 5,
i is a histogram of values of a and TEWL at T0' in test example 5,
j is a plot of the semi-subjective pain scores of volunteers in test example 2 as a function of time,
k is a plot of the semi-subjective pain scores of volunteers over time in example 1,
l is a plot of the semi-subjective pain score of volunteers in test example 5 as a function of time;
fig. 4 is a result chart in effect example 4:
a is a graph of the results of the effect of tape stripping or capsaicin patch on a over time,
b is a graph of the results of the effect of tape stripping or capsaicin patch on TEWL over time,
c is a histogram of values of a and TEWL at T0',
d is a plot of the semi-subjective pain score of volunteers versus time;
fig. 5 is a graph showing the numerical results of the face and forearm a and TEWL in effect example 5;
fig. 6 is a graph showing the results of the sample test in effect example 5:
a is a graph of the effect of the sample on the change of the face a,
b is a graph of the effect of the sample on changes in forearm a,
c is a graph of the effect of the sample on the change in facial TEWL,
d is a graph of the effect of the sample on forearm TEWL variation;
FIG. 7 is a graph showing the effect of the test sample of effect example 5 after application;
FIG. 8 is a graph of semi-subjective evaluation score for volunteers in effect example 5;
fig. 9 is a graph showing the results in effect example 6:
a is a graph of the burning sensation result caused by two evaluation methods,
b is a graph of the results of the trend of the selection of the two evaluation methods.
Detailed Description
For a better description of the objects, technical solutions and advantages of the present invention, the present invention will be further described with reference to the following specific examples.
The reagents, methods and apparatus employed in the present invention are those conventional in the art unless otherwise indicated.
Adhesive tape: medical tape, 2.4cm x 9.8cm,3m company;
capsaicin: beijing Sorbiao technologies Co., ltd;
saffron extract: INCI: water, 1, 3-propanediol, saffron extract, company i.d. bio as;
gentian root extract: INCI: gentian extract, maltodextrin, yunnan component biosystems, inc;
a filter sheet: shanghai Maclin Biochemical technologies Co.
The cosmetics for sensitive skin used in the examples and comparative examples of the present invention were consistent, and the amounts of the cosmetics used per square centimeter of skin were the same.
The data analysis method comprises the following steps: each test was repeated three times using SPPS24.0 software and the data are expressed as mean ± standard deviation. The comparison of the two groups of data adopts a nonparametric T test, the comparison of the data among the groups adopts a variance analysis, ns is more than 0.05, P is less than 0.01, P is less than 0.001, and P is less than 0.0001.
Example 1
The embodiment of the invention provides a method for evaluating the soothing efficacy of a sensitive skin cosmetic, which comprises the following steps:
(1) The inner forearm of the subject was randomly selected as the skin test area using colorimeter CL400 and The TM Hex instrument (courage+khazaka) measures TEWL and a values for the corresponding region;
(2) Peeling the skin test area with medical adhesive tape at 20+ -1deg.C and relative humidity of 40-60% for 5 times, then applying capsaicin patch for 10min, and standing for 10min after treatment; testing redness and transepidermal water loss at the skin after one-time resting;
(3) Applying cosmetics on the skin test area after primary standing, and after application, standing for 20min for the second time, and testing redness and transepidermal water loss of the skin after secondary standing;
(4) Finally, calculating the change rates of a and TEWL according to a calculation method of a value I and a calculation method of a value IV respectively, and calculating the change amounts of a and TEWL according to a value III (A) and a value III (B);
the preparation method of the capsaicin patch comprises the following steps: immersing the filter paper sheet into an ethanol water solution containing 0.01% of capsaicin (the volume ratio of ethanol to water is ethanol: water=10:90), taking out, and directly applying to the skin surface to obtain the capsaicin patch;
the calculation method of the value IV is as follows:
skin redness (a) change rate= (skin redness after one standing-skin redness before treatment)/skin redness before treatment x 100%;
rate of change of skin transepidermal water loss (TEWL) = (skin transepidermal water loss after one rest-skin transepidermal water loss before treatment)/skin transepidermal water loss before treatment x 100%;
The numerical value three (A) calculation method of the invention is as follows:
skin redness change amount = (skin redness after one rest-skin redness after one rest for X min) X (-1);
skin transepidermal water loss (TEWL) change amount= (skin transepidermal water loss after one rest-skin transepidermal water loss after one rest for X min) X (-1);
the calculation method of the numerical value III (B) is as follows:
skin redness change amount = (skin redness after secondary standing-skin redness after primary standing) × (-1);
skin transepidermal water loss (TEWL) change amount= (skin transepidermal water loss after secondary rest-skin transepidermal water loss after primary rest) × (-1).
The calculation method of the first value is as follows:
skin redness (a) change rate= (skin redness after secondary standing-skin redness before treatment)/skin redness before treatment x 100%;
rate of change of skin transepidermal water loss (TEWL) = (skin transepidermal water loss after secondary resting-skin transepidermal water loss before treatment)/skin transepidermal water loss before treatment x 100%.
Example 2
The present example provides a method for evaluating the soothing efficacy of cosmetics for sensitive skin, which differs from example 1 only in that the filter is immersed in an aqueous ethanol solution containing 0.02% capsaicin (volume ratio of ethanol to water is ethanol: water=10:90).
Example 3
The present example provides a method for evaluating the soothing efficacy of cosmetics for sensitive skin, which differs from example 1 only in that the filter is immersed in an aqueous ethanol solution containing 0.005% capsaicin (volume ratio of ethanol to water is ethanol: water=10:90).
Example 4
The present example provides a method for evaluating the soothing efficacy of cosmetics for sensitive skin, which differs from example 1 only in that the filter is immersed in an aqueous ethanol solution containing 0.03% capsaicin (volume ratio of ethanol to water is ethanol: water=10:90).
Example 5
The present example provides a method for evaluating the soothing efficacy of cosmetics for sensitive skin, which differs from example 1 only in that the filter is immersed in an aqueous ethanol solution containing 0.01% capsaicin (volume ratio of ethanol to water is ethanol: water=30:70).
Example 6
The present examples provide a method for evaluating the soothing efficacy of cosmetics for sensitive skin, which differs from example 1 only in that it is treated in an environment of 30.+ -. 1 ℃.
Example 7
The embodiment of the invention provides a method for evaluating the soothing efficacy of cosmetics for sensitive skin, which is only different from embodiment 1 in that the number of times of tape stripping is 2.
Example 8
The embodiment of the invention provides a method for evaluating the soothing efficacy of cosmetics for sensitive skin, which is only different from embodiment 1 in that the number of times of stripping the adhesive tape is 15.
Example 9
The embodiment of the invention provides a method for evaluating the soothing efficacy of cosmetics for sensitive skin, and the evaluation method is only different from embodiment 1 in that the application time of a capsaicin patch is 2 minutes.
Example 10
The embodiment of the invention provides a method for evaluating the soothing efficacy of cosmetics for sensitive skin, and the evaluation method is only different from embodiment 1 in that the application time of a capsaicin patch is 15min.
Example 11
The embodiment of the invention provides a method for evaluating the soothing efficacy of cosmetics for sensitive skin, which is the only difference from embodiment 1 in that the one-time standing time after treatment is 20min.
Example 12
The embodiment of the invention adopts an orthogonal test method to further explore the tape stripping times, capsaicin patch application time and primary standing time, and the orthogonal test design is shown in table 1;
TABLE 1
Number of tape peels/times | Patch application time/min | One-time standing time/min | |
Test example 1 | 5 | 5 | 5 |
Test example 2 | 5 | 8 | 10 |
Test example 3 | 5 | 10 | 15 |
Test example 4 | 10 | 5 | 10 |
Test example 5 | 10 | 8 | 15 |
Test example 6 | 10 | 10 | 5 |
Test example 7 | 15 | 5 | 15 |
Test example 8 | 15 | 8 | 10 |
Test example 9 | 15 | 10 | 10 |
Test examples 1 to 9 were identical to example 1 except for the parameters shown in Table 1.
Comparative example 1
The invention provides a method for evaluating the soothing efficacy of a sensitive skin cosmetic, which comprises the following steps:
using colorimeter CL400 and prior to processingThe TEWL and a values of the corresponding area were measured by TM Hex instrument (courage+khazaka), and then a patch of 0.8cm diameter containing capsaicin (0.01% by mass of capsaicin, 50 μl) was applied to both sides of the nose lip for one-time resting for 8min at a temperature of 20±1 ℃ and a relative humidity of 40-60%; the treated skin was then tested for redness and transepidermal water loss;
then, applying a sensitive skin cosmetic on the skin after primary standing, and carrying out secondary standing for 20min after the application, and testing redness and transepidermal water loss of the skin after secondary standing;
and finally, calculating the change rates of a and TEWL according to the calculation methods of the first value and the fourth value respectively, and calculating the change amounts of a and TEWL according to the third value (A) and the third value (B).
Comparative example 2
The comparative example of the present invention provides a method for evaluating the soothing efficacy of cosmetics for sensitive skin, which does not include the step of applying capsaicin patch, compared with example 1.
Comparative example 3
The comparative example of the present invention provides a method for evaluating the soothing efficacy of cosmetics for sensitive skin, which does not include the step of tape peeling, compared to example 1.
Comparative example 4
The comparative example of the present invention provides a method for evaluating the soothing efficacy of cosmetics for sensitive skin, which comprises applying capsaicin patch for 10min before peeling off the inner side of forearm skin of a subject 5 times using medical adhesive tape, compared with example 1.
Comparative example 5
The comparative example of the present invention provides a method for evaluating the soothing efficacy of cosmetics for sensitive skin, which is different from example 1 only in that the number of tape peels was 20.
Effect example 1
To explore the effect of different arm skin areas on the method of the present invention, experiments were performed on the basis of example 12 and the numerical four calculation method from the following steps:
72 volunteers were divided into 9 groups of 8 persons each, each divided into four parts on the inner side of the double forearm, and the dense distribution of blood vessels was avoided, four 2.5cm×4cm (10 cm) 2 ) The size of the regions are denoted as Z1, Z2, Z3 and Z4, respectively (specific regions are shown in FIG. 1). In particular, a test flow diagram is shown in FIG. 2, using colorimeter CL400 and prior to any operation The TM Hex instrument (courage+khazaka) measures TEWL and a values for the corresponding region, noted as T0. Stripping phase with medical adhesive tapeAfter the number of applications, the patches consisting of filters immersed in 0.01% capsaicin ethanol/water (10%/90%, v/v) were applied for a corresponding time, after which the a and TEWL values of the corresponding areas were measured after standing for a corresponding time, this time point being denoted as T0'. The Coefficient of Variation (CV) for each region a and TEWL values was calculated as cv= (post-injury measured value-initial measured value)/initial measured value, and the consistency of the a values and TEWL CVs in the different test regions under the different combination treatments was analyzed. Subsequently, a region was randomly selected within Z1, Z2, Z3 and Z4 for example 1 treatment and comparison with comparative example 1, and the difference between the two was analyzed, facilitating analysis of subsequent experiments.
Table 2 represents the CV value difference test results of four regions a and the CV value difference test result analysis of four regions TEWL. Table 2 represents the P-value results for four regions a and TEWL. As shown in the table results, the values of P of the CV values of a and TEWL of the 4 regions of the forearm are greater than 0.05, and there is no significant difference, i.e., the values of a and TEWL of the four regions of the forearm have good consistency under different treatments, and the left hand measurement and the right hand measurement are not different, so that the method can be applied to subsequent experimental investigation, i.e., 4 parallel data can be obtained by each person under one treatment mode, 2 parallel data can be obtained by each person under two treatment modes, and one person can perform 4 treatment modes at most.
TABLE 2
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Effect example 2
1. Analysis of the logarithmic value four
The effect examples of the present invention verify the accuracy of the results obtained in examples 1 to 12 and comparative examples 2 to 5 and the acceptability of the evaluation method. Firstly, analyzing a value IV, wherein the value IV is a sensitive skin damage model established by taking a forearm as a model, and the model can prove whether the establishment of the sensitive skin damage model by using the forearm skin can effectively replace facial capsaicin for evaluation, namely the feasibility of the model is verified firstly;
since comparative example 1 is a conventional method for evaluating sensitive skin according to a conventional method and is a conventional method for evaluating sensitive skin at present, the data result obtained in comparative example 1 represents data at the time of actual damage to sensitive skin, and therefore, the data of the value four obtained in examples 1 to 12 and comparative examples 2 to 5 are compared with the data of the value four in comparative example 1 to evaluate the accuracy of the evaluation methods provided in examples 1 to 12 and comparative examples 2 to 5. The number of the tested persons is not less than 8 persons per group in each experiment. Acceptability of the test method was assessed according to a semi-subjective pain table of 5 minutes (0=no sensation, 1=almost detectable, 2=slightly detectable, 3=moderately detectable, 4=severely detectable, 5=pain); the results obtained are shown in Table 3;
In addition, the present invention recruits a total of 72 subjects, including 50 subjects positive for capsaicin (facial capsicum burning grade > 3 minutes) aged 18-50. The tested objects used in the examples, the test examples and the comparative examples are healthy objects, and the skin is not obviously different under the normal state after detection; the healthy volunteers are recruited according to the current advice of Helsinki statement and the basic guidelines of non-substance cultural heritage GCP applicable to cosmetics; subjects with chronic or acute dermatitis during the test period or who have been using topical drugs (such as antibiotics or anti-inflammatory drugs) or oral immunosuppressive drugs during the last 2 weeks were excluded, were not allowed to use cosmetics in the test area 3 days before the study was started, and volunteers were also required to avoid sunbathing, sauna and swimming pools, and intense physical exertion;
all equipment and instrumentation during the test were prepared and handled by trained, experienced testers, and the experiments were performed after volunteers had been adapted to the following conditions for at least 30 min: a relative humidity of 21.+ -. 1 ℃ and 50.+ -. 10%;
TABLE 3 Table 3
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As can be seen from table 3, the technical scheme of the invention, that is, the evaluation method obtained in example 1, and the existing facial capsaicin evaluation method have no statistical difference between the values of redness and transepidermal water loss before and after the evaluation treatment (before and after the establishment of damaged skin), and the consistency between the values is good, which indicates that the evaluation method provided by the invention can effectively replace the existing facial capsaicin patch evaluation method, and has higher prediction accuracy and stability. As can be seen from table 3, the semi-subjective score obtained by the further preferred evaluation method of the present invention is below 4.92 score, which is significantly lower than the score in comparative example 1, i.e., the evaluation method of the present invention is milder, does not cause intolerable pain, and is beneficial for subsequent popularization and use;
As can be seen from examples 1 and comparative examples 2-4, whether the tape stripping step or the capsaicin application step was absent, or the tape stripping and capsaicin application were in the same order, the values for a and TEWL were significantly different from the values for the two indices in comparative example 1, indicating that the two steps were not necessary;
as can be seen from comparative example 1 and examples 2 to 4, the mass percentage of capsaicin in the capsaicin patch has a certain influence on the accuracy of the evaluation method, and when the further preferable mass percentage of capsaicin is 0.005 to 0.02%, especially example 1 is 0.01%, the obtained evaluation method has no significant difference from the numerical value in comparative example 1, i.e., the accuracy is optimal;
as can be seen from comparative example 1 and example 5, the specific component proportions of the solution in the preparation of capsaicin patch also have a certain influence on the accuracy of the evaluation method; as can be seen from comparative examples 1 and 6, the change in the ambient temperature of the treatment also has a certain influence on the accuracy of the evaluation method;
as can be seen from comparative example 1, examples 7 to 11, test examples 1 to 9 and comparative examples 4 to 5, the number of tape peels, the application time, the one-time standing time, the order of application and the like all have an influence on the accuracy of the evaluation method; when the number of tape peels in comparative example 5 was not within the range given in the present invention, the evaluation method was not only remarkably reduced in accuracy, but also when the number of peels reached 20 times, the semi-subjective score reached 4.92 points, i.e., the subject felt pain, and was intolerable.
2. Analysis of logarithmic value three (A)
Further analyzing the value three (A), exploring the relief condition of the forearm and the facial skin in the natural state after injury, and judging whether the physiological condition state of the arm and the facial can be consistent after the method is applied. The 48 healthy volunteers are selected and divided into 6 groups, 8 persons in each group, and the a and TEWL measurement experimental results are shown in tables 4 and 5 respectively; wherein the data after modeling for 10min is data after primary standing;
TABLE 4 Table 4
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TABLE 5
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Note that: with a transverse subscript for the data inflection point.
It can be further seen from tables 4-5 that, with the technical solution of the present invention, the natural state of relaxation of skin with TEWL values after the arm is treated in different ways maintains good consistency with facial skin over time, and it is noted that TEWL has small range of fluctuation due to the influence of respiratory airflow of the subject and the general degree of fitting of the detection instrument to the face detection area during the examination. From the data, it can be seen that the state of natural skin repair of the arm before and after the treatment obtained according to example 1 has good agreement with the trend of the existing face capsaicin evaluation method.
In addition, the analysis of the first value and the second value is carried out in the same way, the analysis of the results shows that the cosmetic for sensitive skin obtained by adopting the technical scheme of the invention is obviously improved compared with a blank treatment group before and after the use, and has good consistency with the existing evaluation result of the face capsaicin.
Effect example 3
Based on the effects of examples 1-2, example 1 was the optimal treatment conditions, and in order to better demonstrate the consistency between example 1 and comparative example 1 under different conditions, further preferred test examples 2 and 5 were conducted based on the value of four, and in order to reduce the measurement time as much as possible, the measurement was conducted uniformly after uniformly selecting a standing time of 10 minutes. The method specifically comprises the following steps:
the 33 volunteers were randomly divided into 3 groups of 11 persons each. Tape stripping was performed simultaneously with the capsaicin patch combination and facial capsaicin patch tests. In the facial capsaicin patch method, filter paper with a diameter of 0.8cm and containing capsaicin (0.01%, 50. Mu.L) was applied to both sides of the nose lip for 8 minutes. When the tape stripping and capsaicin patch combination method was performed, after the corresponding number of stripping, 0.01% capsaicin impregnated patches were applied to Z1, Z2, Z3, Z4. 10, 20, 30, 40, 50 minutes after patch removal, the a-value and TEWL of the corresponding area of the face and forearm are measured respectively, denoted as T0', T1, T2, T3 and T4 respectively, the a-value and TEWL values at T0' are calculated, the values = (post-injury measurement-initial measurement)/initial measurement x 100%; meanwhile, at 6 time points (T0', ti-patch removal time, T1, T2, T3, T4) a 5-point semi-subjective scale (0=no sensation, 1=almost detectable, 2=slightly detectable, 3=moderately detectable, 4=severely detectable, 5=painful) was used for questionnaire;
The results obtained are shown in fig. 3, wherein a, b, c in fig. 3 represent the variation of a and TEWL and its value at T0' in test example 2; d, e, f in fig. 3 represent the change of a and TEWL and its value at T0' in example 1; g, h, i in fig. 3 represent the change of a and TEWL and its value at T0' in test example 5; j, k, l in fig. 3 represent semi-subjective pain scores of volunteers of test example 2, example 1, test example 5; and in the figure, the forearms and the facial data are significantly different (P < 0.05), P < 0.05, and P < 0.001;
as can be seen intuitively from fig. 3d-f, the changes in the combined tape-stripping and capsaicin patch panel a, TEWL and semi-subjective volunteer scores of example 1 exhibited the same stimulus response and natural recovery tendencies as comparative example 1; specifically, the a-value and TEWL are maximum at T1, and then decrease. The values of the a and TEWL values of example 1 for the combined tape peel and capsaicin patch method were not significantly different from comparative example 1; therefore, the evaluation method in example 1 was the most consistent with the test results of comparative example 1.
Effect example 4
To further investigate the effect of individual factors on example 1 at different times, further tests were carried out on the basis of effect example 1 on comparative examples 2 to 3 with the value four as reference, comprising the following steps:
Selecting 20 volunteers, and performing the evaluation procedure in comparative example 2, the evaluation procedure in comparative example 3, and no treatment (blank control), respectively measuring a 'value and TEWL of the corresponding region of the forearm, respectively denoted as T0, T0', T1, T2, T3, and T4, respectively, calculating a 'value and TEWL value at T0', the value= (post-injury measurement value-initial measurement value)/initial measurement value x 100%; meanwhile, at 6 time points (T0', ti-patch removal time, T1, T2, T3, T4) a 5-point semi-subjective scale (0=no sensation, 1=almost detectable, 2=slightly detectable, 3=moderately detectable, 4=severely detectable, 5=painful) was used for questionnaire;
the results obtained are shown in fig. 4, where a in fig. 4 is the effect of tape stripping or capsaicin patch on a; FIG. 4 b is the effect of tape stripping or capsaicin patch on TEWL at various time points; FIG. 4 c is a plot of tape peel or capsaicin patch versus a and TEWL at T0'; fig. 4 d is a semi-subjective pain score of volunteers on tape peel or capsaicin patch; the graph shows a significant difference (P < 0.05) from the initial value at T0.
As can be seen from fig. 4, a significant difference was observed between the tape release group and T0 compared to a x value of T0 only at T0' and T1, while no significant difference was observed between other time points and the blank or initial values of capsaicin patch. No significant differences were found between either T0 or blank, tape peel or capsaicin patch in TEWL assay; it can also be seen from the semi-subjective scores that the tape peel and capsaicin patch burn scores were no more than 2 points, respectively, below the 3 point criterion for facial capsaicin positive results. Thus, the skin response following the combined application of tape release and capsaicin patch in example 1 is not caused by simple tape release or capsaicin patch, emphasizing the necessity of combined use.
Effect example 5
Effect example 5 the magnitude of the soothing effect of a cosmetic for sensitive skin at different times was further investigated, and the soothing emulsion of the test sample provided in this effect example had a unique active ingredient of 2% 4-t-butylcyclohexanol complex [ 4-t-butylcyclohexanol: saffron extract: gentian extract = 1:0.5:0.5 (w/w) ]; the base sample consisted of an alkaline emulsion free of 4-t-butylcyclohexanol complex; wherein, 4-tertiary butyl cyclohexyl alcohol is a TRPV1 antagonist, has been reported to have good relieving effect on stimulation response induced by TRPV1 activation for many times, saffron extract is rich in flavonoid compounds, gentian extract is rich in gentian glycoside, and has stronger anti-inflammatory effect;
the method specifically comprises the following steps: a total of 30 volunteers with capsaicin burning scores above 3 were included in the study. A 2.5cm x 4cm (10 cm) size area was selected on each forearm, and two test areas were established. The initial a-values and TEWL (T0) of the face and forearm were measured prior to testing. Facial capsaicin patch testing was performed on both nasal labia as in comparative example 1, with the patches removed for 8 minutes and the a values and TEWL measured. A combined tape stripping and capsaicin patch test was then performed, i.e., the example 1 treatment (5 tape strips, 10 minutes capsaicin patch application), and after 10 minutes the a values and TEWL (T0') were measured. Calculating the numerical value between T0' and T0 determines whether the modeling is true. The test samples were then randomly applied to the nasal labial fold and forearm side, with the remaining side being the base sample. After 10, 20, 30, 40 minutes (T1, T2, T3, T4), the test zones were examined for a and TEWL values. The ability of the two samples to relax stimulus and improve redness is represented by a and the number two (B) of TEWL values; meanwhile, at 4 time points (T1, T2, T3, T4), a 5-point semi-subjective scale (0=no sensation, 1=almost detectable, 2=slightly detectable, 3=moderately detectable, 4=severely detectable, 5=painful) was used for questionnaire;
The results obtained are shown in fig. 5-8, wherein fig. 5 is a graph of the numerical results of facial and forearm a and TEWL, fig. 6a and b are graphs of the effect of the sample on the change in facial and forearm a, and fig. 6 c and d are graphs of the effect of the sample on the change in facial and forearm TEWL; FIG. 7 is a graph showing the effect of the test sample after application; FIG. 8 is a plot of semi-subjective assessment scores for volunteers; wherein, represent that the test sample differs significantly from the base sample (P < 0.05);
as can be seen from fig. 5, example 1 has good consistency with comparative example 1, i.e., there is no significant difference between the two groups after the tape stripping and the combined capsaicin patch method and the facial capsaicin patch method are examined, the method is successfully established and has good stability; as can be seen from fig. 6, after 10 minutes of facial application of the sample, the a value starts to drop (fig. 6 a), within 10-30 minutes, there is a significant difference between the test sample and the base sample (P < 0.05), 10 minutes to 40 minutes after the sample is applied to the forearm, the variation between the test sample and the base sample is significantly different (fig. 6 b), and there is no significant difference between the test of the face or the forearm and the base sample, so the test result of the present invention is that the skin redness relieving effect of the sample is superior to that of the base sample, there is no significant effect on the TEWL value, and the limitation of the experimental instrument is exactly the same as the comparison result of the facial test; and as can be seen more intuitively from fig. 7, the test sample can relieve stimulated reaction and improve red swelling; as can be seen from fig. 8, at Ti and T0', forearm burning pain was less than facial burning pain, and the experimental sample had a stronger relief from burning pain than the base sample; the results also show that the evaluation method provided by the invention can effectively evaluate the relieving effect of the cosmetics for sensitive skin, obviously lighten the uncomfortable feeling of a subject, has more relieving test method and higher applicability, and further guides the development of the relieving active product.
Effect example 6
The volunteers in effect examples 1-5 were subjected to a willingness questionnaire, and the willingness degree of the capsaicin patch and adhesive tape stripping combination method in example 1 of the invention was compared with that of comparative example 1 (namely, the facial capsaicin patch test method in the prior art), and the obtained statistical results are shown in fig. 9, wherein a in fig. 9 represents the burning pain perception of the volunteers caused by the two evaluation methods, and b in fig. 9 represents the selection trend of the volunteers for the two evaluation methods; as can be seen from fig. 9, a total of 94.00% of volunteers reported a stronger discomfort after treatment with the evaluation method of comparative example 1 (fig. 9 a), up to 96.00% of volunteers were more willing to participate in the test of example 1 (combined tape stripping and capsaicin patch method) (fig. 9 b). These data demonstrate that volunteers have higher compliance with the combined tape stripping and capsaicin patch method, i.e., the evaluation method provided by the invention has higher acceptability.
Finally, it should be noted that the above-mentioned embodiments illustrate rather than limit the scope of the invention, and that those skilled in the art will understand that changes can be made to the technical solutions of the invention or equivalents thereof without departing from the spirit and scope of the technical solutions of the invention.
Claims (15)
1. A method of evaluating soothing efficacy for sensitive skin products, the method comprising the steps of:
(1) Randomly selecting a skin test area on the forearm of a subject, and testing redness and transepidermal water loss of the skin test area;
(2) Sequentially using adhesive tape stripping and capsaicin patch to treat the skin test area, standing for one time after treatment, and testing redness and transepidermal water loss of the skin test area after one-time standing;
(3) Smearing sensitive skin products on the skin test area after primary standing, and after smearing, carrying out secondary standing, and testing redness and transepidermal water loss of the skin test area after secondary standing;
(4) Comparing and calculating the redness and the transepidermal water loss obtained by the test in the step (3) and the step (1) to obtain a first numerical value of the redness and the transepidermal water loss of the skin test area; and/or calculating the redness and the transepidermal water loss obtained by the tests in the step (3) and the step (2) to obtain a second numerical value of the redness and the transepidermal water loss of the skin test area;
(5) Evaluating the soothing efficacy of the product according to the first value and/or the second value;
in the step (2), the number of times of stripping the adhesive tape is 2-15 times; the application time of the capsaicin patch is 2-15min.
2. The method of evaluation of claim 1, wherein the skin test area is selected from the skin at the inner side of the forearm.
3. The method of evaluating according to claim 1, wherein the number of times the tape is peeled off is 2 to 10.
4. The method according to claim 3, wherein the number of times the tape is peeled off is 5 to 10.
5. The method for evaluating according to claim 1, wherein the capsaicin patch is prepared by: the filter paper sheet is immersed in an ethanol water solution containing capsaicin, and can be directly applied to the skin surface after being taken out, namely the capsaicin patch.
6. The method according to claim 5, wherein the mass percentage of capsaicin in the aqueous ethanol solution containing capsaicin is 0.005-0.03%.
7. The method according to claim 6, wherein the mass percentage of capsaicin in the aqueous ethanol solution containing capsaicin is 0.01%.
8. The method according to claim 5, wherein the volume ratio of ethanol to water in the capsaicin-containing aqueous ethanol solution is ethanol: water= (5-15): (85-95).
9. The method of evaluating according to claim 1, wherein the capsaicin patch is applied for 2 to 10 minutes.
10. The method of evaluating according to claim 9, wherein the capsaicin patch is applied for 5 to 10 minutes.
11. The method according to claim 1, wherein the time for one standing is 5 to 20 minutes.
12. The method according to claim 11, wherein the time for one standing is 10 to 15 minutes.
13. The method according to claim 1, wherein the time for the secondary standing is 10 to 40 minutes.
14. The method of claim 1, wherein the treatment is performed at an ambient temperature of 20-25 ℃ and a relative humidity of 40-60%.
15. Use of the method for evaluating the soothing efficacy against sensitive skin products according to any of claims 1 to 14 in soothing active cosmetics.
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